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Urothelial Carcinoma of the BladderPhase 2NCT02710734

Risk Enabled Therapy After Initiating Neoadjuvant Chemotherapy for Bladder Cancer (RETAIN)

A Phase 2 study testing Methotrexate, Vinblastine and Doxorubicin in people with Urothelial Carcinoma of the Bladder, run by Fox Chase Cancer Center at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The aim of this study is to evaluate a risk-adapted approach to the treatment of muscle invasive bladder cancer. Each baseline transuretheral resection of bladder tumor (TURBT) sample will be sequenced while proceeding with neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC)… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma of the Bladder
What is being tested?
Methotrexate, Vinblastine and Doxorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
4 sitesUnited States
Study dates
24 Feb 2016to Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients ≥18 years.
  • Primary urothelial or predominantly urothelial carcinoma of the bladder.
  • Histologic evidence of muscularis propria invasion.
  • AJCC27 clinical stage T2-T4a .
  • No radiographic evidence of lymph node positivity (N0) or metastatic disease (M0). Clinical lymphadenopathy on staging CT greater than 1.5 cm in short axis must be biopsy proven negative.
  • ECOG performance status 0, 1, or 2.
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  • Left ventricular ejection fraction ≥ 50% by MUGA or ECHO within 6 months of study entry.
  • Normal organ and bone marrow function as defined:
  • Leukocytes ≥ 3,000/mcL Absolute neutrophil count ≥ 1,500/mcL Platelets ≥ 100,000/mcL Total bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN Creatinine Creatinine Clearance ≥ 50 mL/min (calculated using the Cockroft-Gault formula or measured with 24 hour urine collection)

Who cannot join

  • Any component of small cell histology.
  • Prior pelvic radiation therapy or patients who have undergone prior radiation to greater than or equal to 25% of the bone marrow within the past year are excluded due to risk of life threatening myelosuppression
  • Prior systemic chemotherapy; patients who have received any previous systemic chemotherapy or radiation therapy for urothelial carcinoma or cytotoxic chemotherapy for another malignancy within 1 year of study entry are ineligible.
  • Prior or concurrent malignancy of any other site except for non-melanoma skin cancer, unless disease free interval ≥ 5 years.
  • Patients who have received experimental agents within 4 weeks of study entry.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Methotrexate, Vinblastine, Adriamycin or Cisplatin or other agents used in the study
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  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined by current oral or intravenous antibiotic therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study due to the potential for teratogenic or abortifacient effects of cytotoxic chemotherapy.
  • Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cytotoxic chemotherapy. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
  • Patients with hydronephrosis that has not been addressed with an intervention such as placement of a stent.
  • Pregnancy \& Women of Childbearing Potential

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Johns Hopkins

    Baltimore, Maryland, 21287

  • Sidney kimmel Cancer Center

    Philadelphia, Pennsylvania, 19107

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Washington Cancer Institute at MedStar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: A Phase II Trial of Risk Enabled Therapy After Initiating Neoadjuvant Chemotherapy for Bladder Cancer (RETAIN BLADDER)

The aim of this study is to evaluate a risk-adapted approach to the treatment of muscle invasive bladder cancer. Each baseline transuretheral resection of bladder tumor (TURBT) sample will be sequenced while proceeding with neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) chemotherapy. Based on the mutational profile and the post AMVAC TURBT findings, patients will be treated with active surveillance (experimental arm), or standard of care intravesicle therapy, chemoradiation or surgery. We hypothesize that this approach will lead to non-inferior metastasis-free survival at 2 years, while preserving the bladder and thus quality-of-life for a proportion of patients.

Read the detailed description

This phase II trial studies how well maximal transurethral surgery (surgery performed with a special instrument inserted through the urethra) followed by accelerated methotrexate, vinblastine, doxorubicin hydrochloride, cisplatin, and radiation therapy work in treating patients with bladder cancer that has spread to the muscle. Drugs used in chemotherapy, such as methotrexate, vinblastine sulfate, doxorubicin hydrochloride, and cisplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more tumor cells. Giving combination chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Being tested
Methotrexate, Vinblastine, Doxorubicin, Cisplatin, Intensity modulated radiation therapy (IMRT)
Keywords
Urothelial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethotrexateDrug

    Administered Day 1 of each 14 day cycle for 3 cycles

  • VinblastineDrug

    Administered Day 1 of each 14 day cycle for 3 cycles

  • DoxorubicinDrug

    Administered Day 1 of each 14 day cycle for 3 cycles

  • CisplatinDrug

    Administered Day 1 of each 14 day cycle for 3 cycles

  • Intensity modulated radiation therapy (IMRT)Radiation

    2.0 Gy per fraction to the whole bladder plus a margin for a total of 32 fractions (64.0 Gy). Radiation will be administered from Monday to Friday

  • Transurethral Resection of Bladder tumorProcedure or surgery

    Performed at before and after AMVAC and after chemoradiation and intravesicle therapy

  • 5-FUDrug

    Continuous 24hr Intravenous infusion days 1-5 and 16-20 with radiation treatment

  • Mitomycin CDrug

    Intravenous on day 1 with radiation treatment

Study groups in NCT02710734
Study groupRoleWhat they receive
CRTExperimentalTrimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then chemoradiation followed by TURBT#3
Receives: Drug: Methotrexate; Drug: Vinblastine; Drug: Doxorubicin; Drug: Cisplatin; Radiation: Intensity modulated radiation therapy (IMRT); Procedure: Transurethral Resection of Bladder tumor; Drug: 5-FU; Drug: Mitomycin C
SurveillanceExperimentalTrimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then active surveillance
Receives: Drug: Methotrexate; Drug: Vinblastine; Drug: Doxorubicin; Drug: Cisplatin; Procedure: Transurethral Resection of Bladder tumor
Intravesicle therapyExperimentalTrimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then intravesicle therapy followed by TURBT#3
Receives: Drug: Methotrexate; Drug: Vinblastine; Drug: Doxorubicin; Drug: Cisplatin; Procedure: Transurethral Resection of Bladder tumor
Radical CystectomyExperimentalTrimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then cystectomy
Receives: Drug: Methotrexate; Drug: Vinblastine; Drug: Doxorubicin; Drug: Cisplatin; Procedure: Transurethral Resection of Bladder tumor

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Metastasis-free survival (MFS) at 2 years.

    Measured: 24 months

Secondary outcomes (1)

  1. Ability to complete of 3 cycles of neoadjuvant AMVAC and chemoradiation therapy with 5-FU and mitomycin C.

    Measured: Up to 37 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2016 (estimated)
  2. Study start24 Feb 2016
  3. Primary completion27 Nov 2025
  4. Study completionDec 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02710734
Sponsor's protocol ID
GU-086
Other IDs
15-1071
Status last verified
May 2026
First submitted
18 Feb 2016
Last updated
22 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Geynisman DM, Abbosh PH, Ross E, Zibelman MR, Ghatalia P, Anari F, Mark JR, Stamatakis L, Hoffman-Censits JH, Viterbo R, Greenberg RE, Churilla TM, Horwitz EM, Hallman MA, Smaldone MC, Uzzo R, Chen DYT, Kutikov A, Plimack ER. Phase II Trial of Risk-Enabled Therapy After Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer (RETAIN 1). J Clin Oncol. 2025 Mar 20;43(9):1113-1122. doi: 10.1200/JCO-24-01214. Epub 2024 Dec 16.

    PubMed 39680823

  • Jiang DM, Chung P, Kulkarni GS, James ND, Sridhar SS. Lack of Evidence Does Not Equal Lack of Benefit: Neoadjuvant Chemotherapy and Trimodality Therapy in Selected Patients with Muscle-Invasive Bladder Cancer : In response to: Dirk Bohmer and Arne Grun. Lacking Evidence to Recommend Neoadjuvant Chemotherapy and Definitive Radiotherapy in Muscle-Invasive Bladder Cancer. Curr Oncol Rep. 2021 Mar 3;23(3):36. doi: 10.1007/s11912-021-01035-9. No abstract available.

    PubMed 33660142

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Methotrexate, Vinblastine and Doxorubicin in people with Urothelial Carcinoma of the Bladder, run by Fox Chase Cancer Center at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Metastasis-free survival (MFS) at 2 years. (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02710734, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.

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